Characterization of C-kit Positive Intrathymic Stem Cells That Are Restricted to Lymphoid Differentiation

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1993 Oct 1

PMID 7690832

Citations 47

Authors

Y Matsuzaki

J Gyotoku

M Ogawa

S Nishikawa

Y Katsura

G Gachelin

H Nakauchi

Affiliations

Soon will be listed here.

Abstract

We found that c-kit-positive, lineage marker-negative, Thy-1lo cells are present in both bone marrow and thymus ("BM c-kit" and "thymus c-kit" cells). Although the two cell types are phenotypically similar, only BM c-kit cells showed the potential to form colonies in vitro as well as in vivo. However, both of them revealed extensive growth and differentiation potential to T cells after direct transfer into an irradiated adult thymus, or a deoxyguanosine-treated fetal thymus. Time course analysis showed that thymus c-kit cells differentiated into CD4CD8 double-positive cells approximately 4 d earlier than BM c-kit cells did. In addition, anti-c-kit antibody blocked T cell generation of BM c-kit cells but not of thymus c-kit cells. Intravenous injection of thymus c-kit resulted in the generation of not only T cells, but B as well as NK1.1+ cells. These data provide evidence that thymus c-kit cells represent common lymphoid progenitors with the differentiation potential to T, B, and possibly NK cells. The c-kit-mediated signaling appears to be essential in the transition from BM c-kit to thymus c-kit cells.

Citing Articles

Distinct subpopulations of DN1 thymocytes exhibit preferential γδ T lineage potential.

Oh S, Liu X, Tomei S, Luo M, Skinner J, Berzins S Front Immunol. 2023; 14:1106652.

PMID: 37077921 PMC: 10106834. DOI: 10.3389/fimmu.2023.1106652.

Zeb1 modulates hematopoietic stem cell fates required for suppressing acute myeloid leukemia.

Almotiri A, Alzahrani H, Menendez-Gonzalez J, Abdelfattah A, Alotaibi B, Saleh L J Clin Invest. 2020; 131(1).

PMID: 33108352 PMC: 7773410. DOI: 10.1172/JCI129115.

Thymic B cell development is controlled by the B potential of progenitors via both hematopoietic-intrinsic and thymic microenvironment-intrinsic regulatory mechanisms.

Xiao S, Zhang W, Manley N PLoS One. 2018; 13(2):e0193189.

PMID: 29462202 PMC: 5819817. DOI: 10.1371/journal.pone.0193189.

The development of T cells from stem cells in mice and humans.

Famili F, Wiekmeijer A, Staal F Future Sci OA. 2017; 3(3):FSO186.

PMID: 28883990 PMC: 5583695. DOI: 10.4155/fsoa-2016-0095.

Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors.

Kobayashi M, Nabinger S, Bai Y, Yoshimoto M, Gao R, Chen S Stem Cells. 2016; 35(4):1053-1064.

PMID: 28009085 PMC: 5367971. DOI: 10.1002/stem.2559.

References

Koo G, Dumont F, TUTT M, Hackett Jr J, Kumar V . The NK-1.1(-) mouse: a model to study differentiation of murine NK cells. J Immunol. 1986; 137(12):3742-7. View

Lowry P, Zsebo K, Deacon D, Eichman C, Quesenberry P . Effects of rrSCF on multiple cytokine responsive HPP-CFC generated from SCA+Lin- murine hematopoietic progenitors. Exp Hematol. 1991; 19(9):994-6. View

Mathieson B, Fowlkes B . Cell surface antigen expression on thymocytes: development and phenotypic differentiation of intrathymic subsets. Immunol Rev. 1984; 82:141-73. DOI: 10.1111/j.1600-065x.1984.tb01121.x. View

Mazda O, Watanabe Y, Gyotoku J, Katsura Y . Requirement of dendritic cells and B cells in the clonal deletion of Mls-reactive T cells in the thymus. J Exp Med. 1991; 173(3):539-47. PMC: 2118807. DOI: 10.1084/jem.173.3.539. View

Till J, McCulloch E . A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961; 14:213-22. View

Guidos C, Weissman I, Adkins B . Intrathymic maturation of murine T lymphocytes from CD8+ precursors. Proc Natl Acad Sci U S A. 1989; 86(19):7542-6. PMC: 298101. DOI: 10.1073/pnas.86.19.7542. View

Wineman J, Gilmore G, Gritzmacher C, Torbett B, Muller-Sieburg C . CD4 is expressed on murine pluripotent hematopoietic stem cells. Blood. 1992; 80(7):1717-24. View

Mulder K, Mulder J . Ketamine and xylazine anesthesia in the mouse. Vet Med Small Anim Clin. 1979; 74(4):569-70. View

Wu L, Antica M, Johnson G, Scollay R, Shortman K . Developmental potential of the earliest precursor cells from the adult mouse thymus. J Exp Med. 1991; 174(6):1617-27. PMC: 2119056. DOI: 10.1084/jem.174.6.1617. View

10.

Bradley T, Hodgson G . Detection of primitive macrophage progenitor cells in mouse bone marrow. Blood. 1979; 54(6):1446-50. View

11.

Boswell H, Wade Jr P, Quesenberry P . Thy-1 antigen expression by murine high-proliferative capacity hematopoietic progenitor cells. I. Relation between sensitivity to depletion by Thy-1 antibody and stem cell generation potential. J Immunol. 1984; 133(6):2940-9. View

12.

Matsumoto K, Yoshikai Y, Moroi Y, Asano T, Ando T, Nomoto K . Two differential pathways from double-negative to double-positive thymocytes. Immunology. 1991; 72(1):20-6. PMC: 1384330. View

13.

Jutila M, Kroese F, Jutila K, Stall A, Fiering S, Herzenberg L . Ly-6C is a monocyte/macrophage and endothelial cell differentiation antigen regulated by interferon-gamma. Eur J Immunol. 1988; 18(11):1819-26. DOI: 10.1002/eji.1830181125. View

14.

Moore M, Owen J . Experimental studies on the development of the thymus. J Exp Med. 1967; 126(4):715-26. PMC: 2138391. DOI: 10.1084/jem.126.4.715. View

15.

Crispe I, Moore M, Husmann L, Smith L, Bevan M, Shimonkevitz R . Differentiation potential of subsets of CD4-8- thymocytes. Nature. 1987; 329(6137):336-9. DOI: 10.1038/329336a0. View

16.

Scollay R, Wilson A, DAmico A, Kelly K, Egerton M, Pearse M . Developmental status and reconstitution potential of subpopulations of murine thymocytes. Immunol Rev. 1988; 104:81-120. DOI: 10.1111/j.1600-065x.1988.tb00760.x. View

17.

Dialynas D, Wilde D, Marrack P, Pierres A, Wall K, Havran W . Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983; 74:29-56. DOI: 10.1111/j.1600-065x.1983.tb01083.x. View

18.

Rodewald H, Moingeon P, Lucich J, Dosiou C, Lopez P, Reinherz E . A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells. Cell. 1992; 69(1):139-50. DOI: 10.1016/0092-8674(92)90125-v. View

19.

Coffman R . Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development. Immunol Rev. 1982; 69:5-23. DOI: 10.1111/j.1600-065x.1983.tb00446.x. View

20.

Frederickson G, BASCH R . L3T4 antigen expression by hemopoietic precursor cells. J Exp Med. 1989; 169(4):1473-8. PMC: 2189248. DOI: 10.1084/jem.169.4.1473. View